Association of plasma levels of soluble receptor for advanced glycation end products and risk of kidney disease: the Atherosclerosis Risk in Communities study.

Background: Advanced glycation end products and their cell-bound receptors are thought to mediate the adverse effects of vascular disease through oxidative stress, inflammation and endothelial dysfunction. We examined the association between the soluble form of receptor for advanced glycation end products (sRAGE) and kidney disease.

Methods: In this case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) study, baseline sRAGE levels were measured in a cohort random sample of participants without kidney disease (n= 1218), and among participants who developed incident chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and ≥25% eGFR decline, n = 151] and end-stage renal disease (ESRD) [entry in the US Renal Data System (USRDS) registry, n = 152].

Results: Baseline sRAGE levels were inversely related to baseline eGFR (r = -0.13). After adjusting for age, sex and race, one interquartile range higher log10-transformed sRAGE was associated with development of CKD [odds ratio: 1.39; 95% confidence interval (95% CI) 1.06-1.83; P = 0.02] and ESRD (hazard ratio: 1.97; 95% CI 1.47-2.64; P < 0.001). These associations were not significant after eGFR adjustment.

Conclusions: High sRAGE levels are associated with incident CKD and ESRD risk, but not after adjustment for kidney function at baseline. Future studies are needed to investigate specific mechanisms underlying the association of sRAGE with kidney disease risk.